EVIDENCE FOR A CATABOLIC ROLE OF GLUCAGON DURING AN AMINO-ACID LOAD

Despite the strong association between protein catabolic conditions an d hyperglucagonemia, and enhanced glucagon secretion by amino acids (A A), glucagon's effects on protein metabolism remain less dear than on glucose metabolism. To clearly define glucagon's catabolic effect on p rotein metabolism during AA load, we studied the effects of glucagon o n circulating AA and protein dynamics in six healthy subjects. Five pr otocols were performed in each subject using somatostatin to inhibit t he secretion of insulin, glucagon, and growth hormone (GH) and selecti vely replacing these hormones in different protocols. Total AA concent ration was the highest when glucagon, insulin, and GH were low. Select ive increase of glucagon levels prevented this increment in AA. Additi on of high levels of insulin and GH to high glucagon had no effect on total AA levels, although branched chain AA levels declined. Glucagon mostly decreased glucogenic AA and enhanced glucose production. Endoge nous leucine flux, reflecting proteolysis, decreased while leucine oxi dation increased in protocols where AA were infused and these changes were unaffected by the hormones. Nonoxidative leucine flux reflecting protein synthesis was stimulated by AA, but high glucagon attenuated t his effect. Addition of GH and insulin partially reversed the inhibito ry effect of glucagon on protein synthesis. We conclude that glucagon is the pivotal hormone in amino acid disposal during an AA toad and, b y reducing the availability of AA, glucagon inhibits protein synthesis stimulated by AA, These data provide further support for a catabolic role of glucagon at physiological concentrations.